Disease relevance of EIF2C1

• Anti-Su autoantibodies from both human patients with rheumatic diseases and a mouse model of autoimmunity recognize the endonucleolytic Argonaute and Dicer proteins, both crucial enzymes of the RNAi pathway [1].

High impact information on EIF2C1

• Argonaute proteins are key players in gene silencing involving small RNAs [2].
• Hallmarks of small RNAs are their dependence on double-stranded RNAs (dsRNA)-specific RNase III-type enzymes for biogenesis and their association with Argonaute family proteins for the silencing process [3].
• The Argonaute family: tentacles that reach into RNAi, developmental control, stem cell maintenance, and tumorigenesis [4].
• Biochemical analysis indicates that AIN-1 interacts with protein complexes containing an Argonaute protein, Dicer, and miRNAs [5].
• The developmental timing regulator AIN-1 interacts with miRISCs and may target the argonaute protein ALG-1 to cytoplasmic P bodies in C. elegans [5].

Biological context of EIF2C1

• The human EIF2C1 gene belongs to a multigene family in human [6].
• The human EIF2C1 gene consists of 19 exons and 18 introns that span a region of almost 50 kb [6].
• Identification of eight members of the Argonaute family in the human genome small star, filled [7].
• Effects of Dicer and Argonaute down-regulation on mRNA levels in human HEK293 cells [8].
• Here we demonstrate that Argonaute proteins--the signature components of the RNA interference (RNAi) effector complex, RISC--localize to mammalian P-bodies [9].

Anatomical context of EIF2C1

• A number of genes have been identified as members of the Argonaute family in various nonhuman organisms and these genes are considered to play important roles in the development and maintenance of germ-line stem cells [7].
• PCR analysis using human multitissue cDNA panels indicated that all four members of the PIWI subfamily are expressed mainly in the testis, whereas all four members of the eIF2C/AGO subfamily are expressed in a variety of adult tissues [7].
• To understand the biological function of the different Ago proteins, we set out to determine if Ago1 through Ago4 are associated with miRNAs as well as RISC activity in human cell lines [10].
• Drosophila Me31B is shown to participate (1) with an FMRP-associated, P body protein (Scd6p/trailer hitch) in FMRP-driven, argonaute-dependent translational repression in developing eye imaginal discs; (2) in dendritic elaboration of larval sensory neurons; and (3) in bantam miRNA-mediated translational repression in wing imaginal discs [11].
• A fraction of Argonaute proteins and miRNAs biochemically cosediment with polyribosomes, yet another fraction paradoxically accumulates in ribosome-free processing bodies (PBs) in the cytoplasm [12].

Associations of EIF2C1 with chemical compounds

• Function of the Trypanosome Argonaute 1 protein in RNA interference requires the N-terminal RGG domain and arginine 735 in the Piwi domain [13].

Regulatory relationships of EIF2C1

• Further investigation revealed that nuclear import of the mitosis-inducing phosphatase Cdc25 is inhibited by overexpression of the Ago1 amino terminus [14].

Other interactions of EIF2C1

• We postulate that at least some members of the human Argonaute family may be involved in the development and maintenance of stem cells through the RNA-mediated gene-quelling mechanisms associated with DICER [7].
• Involvement of AGO1 and AGO2 in mammalian transcriptional silencing [15].
• Particularly, microRNA (miRNA)-mediated translational repression involving PIWI/Argonaute family proteins has been widely recognized as a novel mechanism of gene regulation [16].
• Here, we show that the Argonaute proteins physically interact with a key P-/GW-body subunit, GW182 [17].

Analytical, diagnostic and therapeutic context of EIF2C1

• Immunoprecipitation and affinity binding experiments using human HEK293 cells cotransfected with cDNAs for FLAG-tagged DICER, a member of the ribonuclease III family, and the His-tagged members of the Argonaute family suggested that the proteins from members of both subfamilies are associated with DICER [7].
• Multiple Argonaute sub-families can be identified phylogenetically yet, despite this diversity, molecular and sequence analyses show that Argonaute proteins share common molecular properties and the capacity to function through a common mechanism [18].

References